Genetic study reveals how common tumor suppressor gene affects cancer progression

A UCLA-led genetic study suggests Gene2. 0 (MITF2) can be a driver of tumor progression and extended survival in several common types of cancer. The study could advance the ability to identify genotypephenotype differences that impact clinical outcomes and enable targeted drug development.

Results of the Duke Cancer Institutes 150th Annual Meeting were published in Cell Reports Neuroscience and presented at the 60th Annual Meeting in San Diego.

There are some cancers that do not respond to drugs and theyre often diagnosed in later stages said senior author James Hickman Ph. D. vice president for Epigenetics and Oncology at the Duke Cancer Institute. Glioblastoma is one such cancer and were treating it almost exclusively with ART. But incredibly in about 10 percent of patients the tumor recurs or shows up and then goes on to become more aggressive.

MITF2 a gene involved in triggering a biosystem that stimulates the formation of new membrane potentials is considered a tumor suppressor gene. The researchers showed that the gene is activated in a wide variety of cancers and that MITF2 expression is not reduced in elective bladder cancer which is the most common aggressive brain tumor in adults but increased in many-drug-resistant melanoma non-small cell lung cancer and gastric cancer.

Next the researchers hope to examine the effect of MITF2 in combination with other tumor suppressors to get a broader perspective on how tumors may respond to different types of cancer treatments.

We dont want to just study individual cancers with genetic testing said study senior author and Mendel Professor Bruce Haidle Ph. D. director of the UCLA Laboratory of Molecular Biology Services.

One implication from the findings is that future therapies designed to boost MITF2 as well as other genes linked to cancer cell behavior may potentially require enhanced forms of ART including vaccines or proteomic assays that boost MITF2 expression. Combinations of both approaches could also be helpful in identifying antibiotic-resistant tumors the scientists noted.

This study helps us understand MITF2 but also helps us understand how tumors may respond to targeted and complex drug combinations Haidle said.

Most findings are examples of the work in Haidles lab.

MITF2 is a tumor suppressor Hickman said. I think its inspiring that they sought to study it so broadly and find so many insights and a couple of novel therapeutic possibilities.